Enantiospecific synthesis and cytotoxicity evaluation of ligudentatol: a programmed aromatization approach to the 2,3,4-trisubstituted phenolic motif via visible-light-mediated group transfer radical cyclization

Abstract

A facile enantiospecific approach to (+)-ligudentatol (1) and (-)-ligudentatol (ent-1) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible-light-mediated radical seleno transfer cyclization, bromination, concomitant selenoxide elimination-dehydrobromination, and demethoxycarbonylation, namely, a programmed aromatization. Biological evaluation of the enantiomers of ligudentatol obtained by the present route revealed for the first time their cytotoxicity towards various cancer cell lines.

Keywords: cytotoxicity; natural products; radical reactions; seleno transfer; total synthesis.